1. Field
The present invention relates to a composition for the prevention or treatment of eye diseases. More particularly, the present invention relates to a composition comprising S-allyl-L-cysteine as an active ingredient useful for preventing or treating eye diseases.
2. Description of the Related Art
The macula or macula lutea is a nerve tissue positioned near the center of the retina of the human eye, and is highly responsible for the vision of the eye because it is the center of the visual field where images fall, and it is where most visual cells are concentrated. Macular degeneration (MD), caused by various factors, is a medical condition that results in visual impairment. Macular degeneration is one of the three leading causes of irreversible blindness, together with glaucoma, and diabetic retinopathy.
Macular degeneration occurs largely in dry and wet forms. Dry macular degeneration is a major cause of blindness and visual impairment in older adults. The dry form of macular degeneration leads to atrophy of the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye. In wet macular degeneration, which accounts for much fewer diagnosed cases than those of the dry form, abnormal blood vessel growth can form beneath the macula; these vessels can leak blood and fluid into the macula and damage photoreceptor cells. Caused by vessels, hemorrhage, fluid, and scarring, the wet form of macular degeneration can progress rapidly and over time cause severe damage to central vision.
Age-related macular degeneration (AMD), although its etiology is yet unknown, is known to exhibit the age-associated, excessive accumulation of pigment in retinal pigment epithelial (RPE) cells in its early stages. Representative among pigment deposits in RPE cells is N-retinylidene-N-retinyl-ethanolamine (A2E), which is synthesized by conjugating all-trans retinal with ethanolamine. A2E accumulates in RPE cells of the eye, and generates singlet oxygen upon photoexcitation, which leads to an oxidation-associated loss of double bond conjugation, causing damage to RPE cells.
To date, a complete therapy for age-related macular degeneration is difficult to expect mainly because the exact mechanism of macular degeneration is still unknown. It is thus important to appropriately prevent or minimize vision loss caused by the progress of macular degeneration. Recent discoveries have applied antioxidant vitamins and zinc (Zn) to the therapy of age-related macular degeneration because of their ability to prevent the progression of macular degeneration. For the wet form of age-related macular degeneration, early laser treatment can reverse the formation of new blood vessels, thus preventing aggravation of the disease. However, these therapies do not yet guarantee satisfactory results. Currently, prophylaxis is most important in treating age-related macular degeneration.
The accumulation of lipofuscin, which is the name given to lipid-containing, finely granular yellow-brown pigment granules in retinal pigment epithelial cells is known to closely correlate with the onset of atrophic macular degeneration that accounts for a significant portion of diagnosed age-related macular degeneration cases, as demonstrated by many studies.
According to day-to-day variations in life, retinal pigment epithelial cells digest optic discs of photoreceptors of rod cells in the daytime, and optic discs of photoreceptors of cone cells at night, with concomitant production of lipofuscin as a residue of lysosomal digestion. In addition, retinal pigment epithelial cells phagocytizes adjacent, dysfunctional retinal pigment epithelial cells and photoreceptors, which adds to the load of lipofuscin accumulation. Lipofuscin is composed mainly of non-degradable, bis-retinoid adducts and is produced via the following biosynthesis pathway: 1) photoreceptor cells, which absorb light in the retina, produce vitamin A aldehyde (all-trans-retinal) from 11-cis-retinal by photoisomerization; 2) the all-trans-retinal is transferred from the photoreceptors to retinal pigment epithelium where it is converted into a lipofuscin fluorophore by a series of condensation reactions. The lipofuscin fluorophore mediates light-dependent lipid peroxidation, which may damage retinal cells, resulting in a loss of vision, and even blindness. Lipofuscin fluorophore is generated mainly in postmitotic cells (e.g., cardiomuscular cells, neurons, retinal epithelial cells, etc.) where active metabolism occurs. Examples of the lipofuscin fluorophore isolated thus far include A2E and a double bond isomer thereof, Iso-A2E, and an all-trans-retinal dimer conjugate (atRAL dimer).
All of these compounds are generated by phosphate hydrolysis of phosphatidylpyridinium bisretinoid (A2PE), which is generated via the condensation of all-trans-retina and phosphatidylethanolamine, both isolated from the visual cycle. One molecule of all-trans-retinal reacts with phosphatidylethanolamine (PE) to generate the Schiff base N-retinylidene-phosphatidylethanolamine (NRPE), which is found to be a substrate for the photoreceptor-specific ATP-binding cassette transporter ABCA4. NRPE from the normal visual cycle is associated with another molecule of all-trans-retinal to generate A2PE, which is promoted under certain environments, intense light, or oxidative stress (Sparrow et al., Vision Res, 2003. 43(28): 2983-90).
According to a variety of studies, A2E accumulation increases with age, and the compounds undergo singlet oxygen-mediated photo-oxidation under intense light. Also, the photo-oxidative product of A2E was found to be a main factor of age-related macular degeneration that is causative of inflammation, as assayed by immune complementation.
The macular degeneration medication market is divided largely into medicines and health functional foods. In South Korea, Ranibizumab (Lucentis) is the only medicine that is approved and on the market as a therapeutic agent for wet macular degeneration. However, at present there are no therapeutic agents approved to treat dry macular degeneration. Ranibizumab is a humanized monoclonal antibody that recognizes and blocks vascular endothelial growth factor (VEGF) A for neovascular age-related macular degeneration so that vision lowered by wet macular degeneration may be recovered, or is not degraded further. According to clinical trials, however, Genentech warned that Ranibizumab may increase the risk of stroke occurrence. In addition, Ranibizumab is expensive, and is marketed as an intraocular injection that is inconvenient for administration.
Turning to the health functional food field, lutein is solely approved as an individual type. Lutein, which accumulates in the retina, serves as a photoprotectant for the macula leutea from degeneration by maintaining macular pigment levels. However, some research has shown that the long-term use of a supplement containing carotenoid, such as lutein, increases the risk of the onset of lung cancer, particularly in smokers. Hence, it may be dangerous for patients who smoke tobacco to ingest lutein-related products.
In addition, although not approved as functional materials by the KFDA, natural products known to have therapeutic effects on macular degeneration include zeaxanthin, a macular pigment like lutein, and anthocyanins, abundantly found in berries. However, there are insufficient studies on the effect of these compounds on macular degeneration. In recent years, the occurrence of macular degeneration has increased in middle-aged, as well as elderly people, while therapeutic modalities for macular degeneration are sparse. Therefore, there is an urgent need for the development of medicines and health functional foods that are useful for preventing macular degeneration.
Similarly, garlic, belonging to the Allium genus, has attracted keen attention as a natural material because it is known to have antibacterial, antifungal, anti-oxidative, and anticancer activity (Ankri et al., Microbes Infect. 1(2), pp 125-129, 1999). Further, garlic has been shown to effectively prevent thrombosis, inflammation, and oxidative stress (Sener et al., Mol Nutr Food Res., 51(11), pp 1345-1352, 2007). Garlic contains a variety of ingredients including non-sulfur compounds and organosulfur compounds among which are steroid saponins such as eruboside-B that exhibit antifungal and anticancer effects (Matsuura H et al., ChemPharm Bull (Tokyo), 36: 3659-3663, 1988), glycoside fractions that function to lower cholesterol levels (Slowing et al., J Nutr., 131, pp 994S-9S, 2001), and beta-chlorogenin that inhibits platelet aggregation (Rahman K et al., J. Nutr. 2006).
As a natural constituent of mature garlic, S-allyl-L-cysteine is reported to exhibit various pharmaceutical efficacies including a suppressive effect on arteriosclerosis due to its antioxidant activity, and an inhibitory effect on some cancer cell lines (Proceedings of the American Association for Cancer Research, 30, p 181, 1989).
S-Allyl-L-cysteine significantly recovered damaged hepatocytes as assayed in rat models of carbon tetrachloride-induced liver injury (CHOI, Soo Yeon, 2009, Effects of S-Allyl Cysteine on carbon tetrachloride-induced liver injury in rats). Further, S-Allyl-L-cysteine also protects the stomach against Helicobacter pylori (Bang, Sung Hye, 2010, Protective effect of S-allyl-L-cysteine (SAC) on Helicobacter pylori-infected mice).
In Korean Patent Application Unexamined Publication No. 10-2011-0032641 (titled “Composition for preventing or treating gastrointestinal disorders comprising s-allyl-l-cysteine as an active ingredient”), it is disclosed that S-allyl-L-cysteine can suppress the infection of Helicobacter and protect the stomach from Helicobacter-induced damage.
This application may reference various publications by author, citation, and/or L by patent number, including without limitation, articles, presentations, and patents. The disclosures of each of any such references in their entireties are hereby incorporated by reference into this application. However, nowhere is the preventive and therapeutic effect of S-allyl-L-cysteine on age-related macular degeneration mentioned in the articles and patent documents.
Currently, it would be medically difficult to expect a perfect cure for age-related macular degeneration, and therefore, prevention is most important. As disclosed, intensive and thorough research conducted by the present inventors has resulted in the finding that S-allyl-L-cysteine is effectively preventive and curative of age-related macular degeneration.